Interaction of histone Acetylases and deacetylases in vivo
Interaction of histone Acetylases and deacetylases in vivo
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DOI：
10.1128/mcb.23.3.1025-1033.2003
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发表时间：
2003-02-01
影响因子：
5.3
通讯作者：
Ozato, K
中科院分区：
文献类型：
--
作者：
Yamagoe, S;Kanno, T;Ozato, K
组蛋白乙酰化酶（HATs）和去乙酰化酶具有相反的酶活性，它们影响染色质并调节转录。这两种酶的活性被认为是通过一种未知的机制在细胞内保持平衡的，这种机制可能涉及它们的直接相互作用。利用荧光共振能量转移分析，我们证明了乙酰化酶PCAF和组蛋白去乙酰化酶1 （HDAC1）在活细胞中空间接近，与它们的物理相互作用是相容的。在HeLa细胞中，共免疫沉淀实验表明内源性hdac与PCAF和另一种乙酰化酶GCN5相关。我们通过甘油梯度沉降分析发现，HATs被整合到一个大的多蛋白HDAC复合物中，这与先前描述的含有mSin3A、Mi-2/NRD或CoREST的HDAC复合物不同。在体外观察到的直接蛋白质相互作用部分解释了这种HDAC-HAT关联。HDAC-HAT复合物可能在体内建立两种酶的动态平衡中起作用。
Having opposing enzymatic activities, histone acetylases (HATs) and deacetylases affect chromatin and regulate transcription. The activities of the two enzymes are thought to be balanced in the cell by an unknown mechanism that may involve their direct interaction. Using fluorescence resonance energy transfer analysis, we demonstrated that the acetylase PCAF and histone deacetylase 1 (HDAC1) are in close spatial proximity in living cells, compatible with their physical interaction. In agreement, coimmunoprecipitation assays demonstrated that endogenous HDACs are associated with PCAF and another acetylase, GCN5, in HeLa cells. We found by glycerol gradient sedimentation analysis that HATs are integrated into a large multiprotein HDAC complex that is distinct from the previously described HDAC complexes containing mSin3A, Mi-2/NRD, or CoREST. This HDAC-HAT association is partly accounted for by a direct protein-protein interaction observed in vitro. The HDAC-HAT complex may play a role in establishing a dynamic equilibrium of the two enzymes in vivo.